[DSRP Evidence](https://dsrpevidence.org/)

# Dissecting pleiotropy between major depressive disorder and physical disease comorbidities

## Details

**Authors** Woodward et al.

**Year** 2026

**Publisher** Nature Genetics

**Discipline** Genetics

**Secondary disciplines** Medicine

[Read it at the publisher](https://doi.org/10.1038/s41588-026-02735-3) 
10.1038/s41588-026-02735-3

## In authors' words

### What they found (results)

Genomic structural equation modeling identified four physical-disease clusters (cardiovascular, metabolic, gastrointestinal, immune), three of which independently associate with major depressive disorder and jointly explain 47% of its SNP-heritability, with the gastrointestinal cluster showing the strongest genetic correlation, implicating a gut-brain axis mechanism.

## Commentary

### In short

The whole genetic architecture of a disorder is decomposed into distinct disease-cluster categories, and the shared genetic liability between those categories and the disorder constitutes a causal, mechanistic relationship rather than mere co-occurrence.

**Patterns it shows** D, S, R

**Added** 2026-08-27

**How to cite this** Woodward et al. (2026). Dissecting pleiotropy between major depressive disorder and physical disease comorbidities. Nature Genetics.